This international collaborative project responds to PA-15-142 and its call for collaborative research applications on drug abuse and addiction that take advantage of special opportunities that exist outside the United States. It is a mixed methods, longitudinal, and community-based study of the causes and public health consequences of synthetic drug abuse. The main objectives are to: 1) develop and refine a conceptual model of causes and health consequences of synthetic drug abuse; 2) recruit probability samples of drug users and non-users for mixed methods data collection; and 3) analyze the longitudinal mixed methods data to test the conceptual model to enhance our understanding of causes and health consequences of synthetic drug abuse and to identify focal points for effective interventions. There has been an upsurge in the abuse of various synthetic (club) drugs, such as methamphetamine, ketamine, and ecstasy, in China, the United States, and internationally. Unlike that of heroin and opium, use of synthetic drugs often stimulates sexual activities and contributes to unsafe sexual practices and consequently STIs. The potential of the dramatic growth of synthetic drug abuse in fueling the spread of STIs underscores the need to study the etiology of synthetic drug abuse and the link between synthetic drug use and risky sexual behaviors and STIs. The proposed will be the first such focused study in China. Through formative research, the study will develop and refine a conceptual model that integrates sensation seeking, social control, and social learning perspectives on drug abuse and focuses on the neuro-behavioral effects of synthetic drugs and drug use settings on sexual behavior. The overarching hypotheses are that differences in intrapersonal and interpersonal risk/protective factors, interacting with community contextual characteristics, explain why some people use drugs and/or have risky sex while others do not and that neuro-behavioral effects of synthetic drugs (on state/mood), interacting with unique synthetic drug use settings, such as entertainment venues or group gatherings, render users vulnerable to unsafe sex and STIs. The integrated framework and its overarching hypotheses will be empirically tested in community-based samples of 1,920 out-of-treatment synthetic and other drug users and non-drug users age 18 to 39 in Qingdao and Kunming. Data collection will employ mixed methods, integrating in-depth and survey questionnaire interviews and ACASI, and will include biomarkers of STIs and active drug use. To achieve study objectives 1 and 3, data analysis will capitalize on the strengths of the mixed methods, longitudinal data and integrate quantitative (latent class analysis; structural equation modeling; multilevel and mediation/moderation analysis; multiple event analysis, and biomarkers) and qualitative analyses. All analyses will be comparative between the two cities/sites and all quantitative analysis will be appropriately weighted; results will be representative of the target populations i the study sites.